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Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis.

ABSTRACT: Objective: To evaluate the association between biomarkers of innate immunity and the magnetic resonance imaging (MRI) features of earlier and later stages of knee osteoarthritis (KOA). Methods: From 139 and 20 participants with earlier and later stages of KOA, respectively, we analyzed knee MRIs scored using the Boston Leeds Osteoarthritis Knee Score (BLOKS) at recruitment with biomarkers. In paired serum (s) and synovial fluid (sf), we quantified three biomarkers related to innate immunity: lipopolysaccharide binding protein (LBP), CD14 and Toll-like receptor 4 (TLR4), and three proinflammatory biomarkers [interleukin-6 (IL6), IL8, and tumor necrosis factor alpha (TNF?)]. Results: In participants with earlier KOA, (s) LBP was statistically significantly associated with meniscal extrusion, and (sf) CD14 was associated with effusion after adjustment with age, sex, and body mass index. In participants with later stage of KOA, (sf) LBP was associated with effusion. (sf) CD14 was associated with cartilage loss and BML. In earlier stage of KOA, the proinflammatory biomarkers IL6, IL8, and TNF? were associated with most MRI features. Conclusion: Innate immunity biomarkers (s) LBP was associated with MRI meniscal extrusion; (sf) CD14 was associated with MRI synovial inflammation in earlier stage and BMLs in later stage of KOA. Associations between proinflammatory biomarkers and various MRI features in earlier stage of KOA were observed.

SUBMITTER: Rajandran SN

PROVIDER: S-EPMC7689194 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis.

Rajandran Sureka Naidu SN Ma Cheryl Ann CA Tan Jin Rong JR Liu Jin J Wong Steven Bak Siew SBS Leung Ying-Ying YY

Frontiers in medicine 20201112

<b>Objective:</b> To evaluate the association between biomarkers of innate immunity and the magnetic resonance imaging (MRI) features of earlier and later stages of knee osteoarthritis (KOA). <b>Methods:</b> From 139 and 20 participants with earlier and later stages of KOA, respectively, we analyzed knee MRIs scored using the Boston Leeds Osteoarthritis Knee Score (BLOKS) at recruitment with biomarkers. In paired serum (s) and synovial fluid (sf), we quantified three biomarkers related to innate ...[more]

PMID: 33282885

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Project description:BackgroundNonunion is a failure of healing following a bone fracture. Its physiopathology remains partially unclear and the discovery of new mediators could promote the understanding of bone healing.MethodsThirty-three atrophic nonunion (NU) patients that failed to demonstrate any radiographic improvement for 6 consecutive months were recruited for providing serum samples. Thirty-five healthy volunteers (HV) served as the control group. Proteomics studies were performed using SELDI-TOF-MS and 2D-DIGE approaches, associated or not with Proteominer® preprocessing, to highlight biomarkers specific to atrophic nonunion pathology. Peak intensities were analyzed by two statistical approaches, a nonparametric Mann-Whitney U tests (univariate approach) and a machine-learning algorithm called extra-trees (multivariate approach). Validation of highlighted biomarkers was performed by alternative approaches such as microfluidic LC-MS/MS, nephelometry, western blotting or ELISA assays.ResultsFrom the 35 HV and 33 NU crude serum samples and Proteominer® eluates, 136 spectra were collected by SELDI-TOF-MS using CM10 and IMAC-Cu(2+) ProteinChip arrays, and 665 peaks were integrated for extra-trees multivariate analysis. Accordingly, seven biomarkers and several variants were identified as potential NU biomarkers. Their levels of expression were found to be down- or up-regulated in serum of HV vs NU. These biomarkers are inter-α-trypsin inhibitor H4, hepcidin, S100A8, S100A9, glycated hemoglobin β subunit, PACAP related peptide, complement C3 α-chain. 2D-DIGE experiment allowed to detect 14 biomarkers as being down- or up-regulated in serum of HV vs NU including a cleaved fragment of apolipoprotein A-IV, apolipoprotein E, complement C3 and C6. Several biomarkers such as hepcidin, complement C6, S100A9, apolipoprotein E, complement C3 and C4 were confirmed by an alternative approach as being up-regulated in serum of NU patients compared to HV controls.ConclusionTwo proteomics approaches were used to identify new biomarkers up- or down-regulated in the nonunion pathology, which are involved in bone turn-over, inflammation, innate immunity, glycation and lipid metabolisms. High expression of hepcidin or S100A8/S100A9 by myeloid cells and the presence of advanced glycation end products and complement factors could be the result of a longstanding inflammatory process. Blocking macrophage activation and/or TLR4 receptor could accelerate healing of fractured bone in at-risk patients.

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Dataset Information

Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis.

Publications

Exploring the Association of Innate Immunity Biomarkers With MRI Features in Both Early and Late Stages Osteoarthritis.

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